Exp Mol Med.  2011 Jan;43(1):7-14. 10.3858/emm.2011.43.1.001.

Microglial P2X7 receptor expression is accompanied by neuronal damage in the cerebral cortex of the APPswe/PS1dE9 mouse model of Alzheimer's disease

• Lee HG
• Won SM
• Gwag BJ
• Lee YB

• KMID: 991618
• DOI: http://doi.org/10.3858/emm.2011.43.1.001

Abstract

The possibility that P2X7 receptor (P2X7R) expression in microglia would mediate neuronal damage via reactive oxygen species (ROS) production was examined in the APPswe/PS1dE9 mouse model of Alzheimer's disease (AD). P2X7R was predominantly expressed in CD11b-immunopositive microglia from 3 months of age before Abeta plaque formation. In addition, gp91phox, a catalytic subunit of NADPH oxidase, and ethidium fluorescence were detected in P2X7R-positive microglial cells of animals at 6 months of age, indicating that P2X7R-positive microglia could produce ROS. Postsynaptic density 95-positive dendrites showed significant damage in regions positive for P2X7R in the cerebral cortex of 6 month-old mice. Taken together, up-regulation of P2X7R activation and ROS production in microglia are parallel with Abeta increase and correlate with synaptotoxicity in AD.

Keyword

adenosine triphosphate; Alzheimer disease; amyloid beta-protein precursor; Dlgh4 protein, mouse; microglia; reactive oxygen species; receptors, purinergic P2X7

MeSH Terms

Aging
*Alzheimer Disease/genetics/metabolism/pathology
Amyloid beta-Peptides
Animals
Antigens, CD11b/immunology
Blotting, Western
Cerebral Cortex/metabolism/*pathology
Disease Models, Animal
Gene Expression
Mice
Mice, Transgenic
Microglia/*metabolism/pathology
Neurons/metabolism/*pathology
Plaque, Amyloid
Reactive Oxygen Species/*metabolism
Receptors, Immunologic/analysis
Receptors, Purinergic P2X7/*genetics/metabolism